Recombinant Oncolytic Vaccinia Viruses Expressing Human β-Defensin 2 Enhance Anti-tumor Immunity

Cancer is still a leading of cause of death worldwide. Among the bio-therapy strategies for cancer, vaccinia virus (VV) has been widely used as an expression vector because of its potent oncolytic activities in addition to its large capacity for insertion of foreign genes and excellent safety records. In the present study, a novel recombinant VV, VV-HBD2-lacZ, expressing human β-defensin 2 (HBD2), an anti-microbial peptide of the innate immune system, was constructed. First, the chemotaxis characteristics of HBD2 expressed on VV-HBD2-lacZ-infected cells toward dendritic cells (DCs) in vitro and in vivo were demonstrated. The anti-tumor effects of VV-HBD2-lacZ in vitro and in vivo in a mouse melanoma cancer model were then investigated. It was found that VV-HBD2-lacZ was able to inhibit tumor growth and metastasis significantly. It was further demonstrated that VV-HBD2-lacZ induced potent cytotoxic activity by increasing the tumor-infiltrating CD4(+) and CD8(+) T cells. These results indicate that HBD2-expressing VV recruited plasmacytoid DCs (pDCs) to the tumor location, leading to cytotoxic T cell response against the tumor, and thus inhibited tumor growth in vitro and in vivo. In conclusion, oncolytic HBD2-expressing VV provides an effective treatment for tumors by triggering innate and adaptive immunity.